Substantial limitations currently exist in our ability to apply recent biotechnological advances to analyze neural substrates of complex mammalian behavior. In contrast to the rapid pace of innovation seen in the fields of mammalian genomics, medicinal chemistry and information technology, less progress has been made in the development of behavioral assessment techniques for mice or other mammals. Such procedures are vital for exploring the impact of genes, drugs and environment on brain functions relevant to common neuropsychiatric conditions such as schizophrenia, depression, and anxiety. Standard approaches involving repeated removal of mice from their home cages for a battery of behavioral tests are problematic because: 1) they are time-consuming and labor-intensive, 2) the order of test administration can skew the resulting data, 3) removal of mice from the home cage produces stress that confounds interpretation of behavioral data, and 4) data are frequently misinterpreted due to a failure to consider behavioral domains that are not the main focus of study (eg: impact of anxiety on tests of learning).
For example, the 2-bottle ethanol preference test (often used in behavioral phenotyping in alcohol research) is widely used in genetic screens to provide an indication of the rewarding properties of ethanol. The test is simple to administer, but difficult to interpret; increased preference could either reflect enhanced sensitivity to the rewarding properties of ethanol, or alternatively, a reduction of sensitivity requiring animals to consume more ethanol to achieve similar hedonic effects. Moreover, preference for ethanol-containing solutions can be influenced by factors such as taste, novelty and caloric content, and it is often unclear whether animals achieve blood alcohol levels sufficient to produce pharmacological effects. Studies dependent on isolated behavioral outcome measures such as preference are therefore subject to overinterpretation if they are not placed in the context of the multiple neuropsychological processes that influence behavioral performance.
The problem of reliance on isolated behavioral readouts also pertains to apparently simple measures, as indicated by recent findings that the impact of genetic mutations on ethanol-induced motor impairments are highly dependent on the particular behavioral assays employed. In humans, alcohol abuse, dependence and withdrawal occur in a complex behavioral context and produce global perturbations of behavioral organization, including alterations in sleep and vigilance, motor activity levels and coordination, nutrition, anxiety and mood. Behavioral phenotyping approaches are needed that address the complex behavioral contexts in which alcohol consumption occurs, as well as those behaviors that are in turn influenced by alcohol.